Benzinga | Apr 12, 2021 10:14AM EDT

ESSA Pharma Saturday Morning Announced Presentation Of Preclinical Data On Co.'s EPI-7386 At American Association Of Cancer Research Meeting Apr. 10

ESSA Pharma Inc. ("ESSA" or the "Company") (NASDAQ:EPIX), a clinical-stage pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, today presented new preclinical data on ESSA's lead product candidate, EPI-7386, at the 2021 American Association of Cancer Research (AACR) Annual Meeting, which is taking place virtually April 10-15, 2021. EPI-7386 is an investigational, highly selective, oral, small molecule inhibitor of the N-terminal domain of the androgen receptor, which exhibits high potency, low metabolism and on-target specificity.

An e-poster presentation titled, "Comprehensive in vitro characterization of the mechanism of action of EPI-7386, an androgen receptor N-terminal inhibitor" (Abstract number: 1209) was published and available for viewing starting April 10th at 8:30 a.m. ET.

"Previously, we presented in vitro data demonstrating that EPI-7386 binds to the full-length androgen receptor, inhibits the transcription of AR-regulated genes, and physically interacts with the splice variant form AR-V7. Today, we added to these data by demonstrating that EPI-7386 can prevent the androgen receptor from binding to genomic DNA and is active against additional androgen receptor splice variants, including AR-v567es," said Dr. David R. Parkinson, President and Chief Executive Officer, ESSA Pharma, Inc. "These preclinical data suggest EPI-7386 can potentially inhibit AR related transcription, a key driver of prostate cancer, and further supports our ongoing Phase 1 dose escalation study for metastatic-castration resistant prostate cancer patients, which is now dosing patients in the 800 mg cohort."

Dr. David R. Parkinson added, "Our data also showed that EPI-7386, in combination with enzalutamide, may result in broader and deeper inhibition of the AR pathway, underscoring the potential clinical benefit of combining EPI-7386 with current standard-of-care anti-androgen therapies for prostate cancer patients at earlier stages of the disease. We have recently entered into Phase 1/2 trial clinical partnerships with Janssen to evaluate EPI-7386 in combination with apalutamide or with abiraterone acetate + prednisone, as well as with Astellas to evaluate EPI-7386 in combination with enzalutamide."

The studies highlight new information about EPI-7386 including:

* In an in vitro cellular thermal shift assay (CETSA), EPI-7386 was shown to physically interact with both the full-length and the splice variant (AR-V7) form of AR.

* In the cellular model CWR-R1-AD1, driven by full-length AR, EPI-7386 inhibited the transcriptional activity of the AR similar to enzalutamide. EPI-7386 was also active in inhibiting AR transcriptional activity and reducing the cell viability in the AR splice variant AR-v567es-driven cellular model CWR-R1-D567 while enzalutamide showed no activity in this model. The AR-v567es splice variant is a clinically-detected AR splice variant that is constitutively active and is unresponsive to anti-androgens.

* EPI-7386 demonstrated the ability to strongly reduce binding of AR to genomic DNA in a chromatin immunoprecipitation with sequencing (ChIP-seq) assay conducted in the full-length AR driven model LNCaP.

* EPI-7386 exhibits superior activity to enzalutamide in the AR-V7-driven cellular model LNCaP95 by modulating AR-driven gene expression with or without the addition of an external androgen.

* In the full-length AR-driven cellular model LNCaP, EPI-7386 inhibits the androgen regulated transcriptome similar to enzalutamide but with a few notable qualitative and quantitative differences.

* In the same cellular model, combination treatment of EPI-7386 with enzalutamide displayed broader and deeper inhibition of AR-associated transcriptional activity than higher doses of each single agent alone.

* EPI-7386 in combination with 'lutamide molecules, including apalutamide, enzalutamide, and darolutamide, inhibited AR-associated transcriptional activity, demonstrating broader and deeper inhibition of the AR pathway in the AR amplified VCaP cellular model.

The poster is available on AACR's e-poster website and on the "Events & Presentations" section of the Company's website at www.essapharma.com.